Programa de Pós Graduação em Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Laboratório Interdisciplinar de Investigação Médica (LIIM), Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
J Psychiatr Res. 2013 Dec;47(12):1949-54. doi: 10.1016/j.jpsychires.2013.08.019. Epub 2013 Sep 8.
Bipolar disorder (BD) is a severe psychiatric disorder of complex physiopathology that has been associated with a pro-inflammatory state. The aim of the present study was to investigate intracellular pathways associated with inflammatory signaling, assessing the phosphorylation levels of transcription factor nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) in peripheral blood mononuclear cells of euthymic BD patients and healthy controls. Fifteen BD euthymic type I patients, and 12 healthy controls matched by age and gender were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients also by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Phosphorylation levels of p65 NF-κB subunit, and MAPK ERK1/2, and p38 were assessed by Western blot and flow cytometry. Plasma cytokines (IL-2, IL-4, IL6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured using cytometric bead arrays. Western blot and flow cytometry analyses showed increased phosphorylation levels of p65 NF-κB subunit, and MAPKs ERK1/2, and p38 in BD patients in euthymia in comparison with controls. BD patients presented increased pro-inflammatory cytokines levels in comparison with controls, and TNF-α correlated with the levels of phosphorylated p65 NF-κB. The present study found increased activation of MAPK and NF-κB pathways in BD patients, which is in line with a pro-inflammatory status.
双相情感障碍（BD）是一种严重的精神疾病，其病理生理学非常复杂，与炎症状态有关。本研究旨在研究与炎症信号相关的细胞内途径，评估心境正常的 BD 患者和健康对照者外周血单个核细胞中转录因子核因子 kappa B（NF-κB）和丝裂原活化蛋白激酶（MAPKs）的磷酸化水平。本研究纳入了 15 名心境正常的 1 型 BD 患者和 12 名年龄和性别匹配的健康对照者。所有受试者均接受了 Mini-国际神经精神访谈评估，患者还接受了 Young 躁狂评定量表和汉密尔顿抑郁评定量表评估。通过 Western blot 和流式细胞术评估 p65 NF-κB 亚基和 MAPK ERK1/2 及 p38 的磷酸化水平。使用流式细胞术微珠阵列测量血浆细胞因子（IL-2、IL-4、IL6、IL-10、IFN-γ、TNF-α 和 IL-17A）。Western blot 和流式细胞术分析显示，与对照组相比，心境正常的 BD 患者 p65 NF-κB 亚基和 MAPKs ERK1/2 及 p38 的磷酸化水平升高。与对照组相比，BD 患者促炎细胞因子水平升高，且 TNF-α 与磷酸化 p65 NF-κB 水平相关。本研究发现 BD 患者 MAPK 和 NF-κB 途径的激活增加，这与炎症状态一致。
